| Captopril increases the intensity of monocyte infection by Trypanosoma cruzi and induces human T helper type 17 cells. | |
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MedLine Citation:
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PMID: 20964644 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The anti-hypertensive drug captopril is used commonly to reduce blood pressure of patients with severe forms of Chagas disease, a cardiomyopathy caused by chronic infection with the intracellular protozoan Trypanosoma cruzi. Captopril acts by inhibiting angiotensin-converting enzyme (ACE), the vasopressor metallopeptidase that generates angiotensin II and promotes the degradation of bradykinin (BK). Recent studies in mice models of Chagas disease indicated that captopril can potentiate the T helper type 1 (Th1)-directing natural adjuvant property of BK. Equipped with kinin-releasing cysteine proteases, T. cruzi trypomastigotes were shown previously to invade non-professional phagocytic cells, such as human endothelial cells and murine cardiomyocytes, through the signalling of G protein-coupled bradykinin receptors (B(2) KR). Monocytes are also parasitized by T. cruzi and these cells are known to be important for the host immune response during infection. Here we showed that captopril increases the intensity of T. cruzi infection of human monocytes in vitro. The increased parasitism was accompanied by up-regulated expression of ACE in human monocytes. While T. cruzi infection increased the expression of interleukin (IL)-10 by monocytes significantly, compared to uninfected cells, T. cruzi infection in association with captopril down-modulated IL-10 expression by the monocytes. Surprisingly, studies with peripheral blood mononuclear cells revealed that addition of the ACE inhibitor in association with T. cruzi increased expression of IL-17 by CD4(+) T cells in a B(2) KR-dependent manner. Collectively, our results suggest that captopril might interfere with host-parasite equilibrium by enhancing infection of monocytes, decreasing the expression of the modulatory cytokine IL-10, while guiding development of the proinflammatory Th17 subset. |
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Authors:
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J S Coelho dos Santos; C A S Menezes; F N A Villani; L M D Magalhães; J Scharfstein; K J Gollob; W O Dutra |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-21 |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 162 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-12 Completed Date: 2011-03-08 Revised Date: 2013-05-27 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 528-36 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology. |
Affiliation:
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Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Angiotensin-Converting Enzyme Inhibitors / pharmacology* CD4-Positive T-Lymphocytes / drug effects*, immunology, metabolism, parasitology, pathology Captopril / pharmacology* Cells, Cultured Chagas Disease / drug therapy*, immunology, parasitology, physiopathology Gene Expression Regulation Host-Parasite Interactions / drug effects Humans Inflammation Mediators / metabolism Interleukin-10 / biosynthesis, genetics Interleukin-17 / genetics, metabolism Male Monocytes / drug effects*, immunology, metabolism, parasitology, pathology Renin-Angiotensin System / drug effects Th1-Th2 Balance Trypanosoma cruzi / immunology*, pathogenicity Virulence / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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R03 AI066044-03/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Inflammation Mediators; 0/Interleukin-17; 130068-27-8/Interleukin-10; 62571-86-2/Captopril |
| Comments/Corrections | |
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